Cabometyx 20 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

CABOMETYX 20 mg film-coated tablets

CABOMETYX 40 mg film-coated tablets

CABOMETYX 60 mg film-coated tablets

cabozantinib

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

1. What CABOMETYX is and what it is used for
2. What you need to know before taking CABOMETYX
3. How to take CABOMETYX
4. Possible side effects
5. How to store CABOMETYX
6. Contents of the pack and other information

1. What CABOMETYX is and what it is used for

What CABOMETYX is

CABOMETYX is a cancer medicine that contains the active substance cabozantinib. It is used in adults to treat:

• advanced kidney cancer known as advanced renal cell carcinoma
• liver cancer when a specific anticancer medicine (sorafenib) is no longer able to stop the progression of the disease
• advanced neuroendocrine tumours: tumours that originate in the pancreas, stomach, intestines, lung or other organs. It is given when patients with these tumours no longer respond to a previous treatment option.

CABOMETYX is also used to treat locally advanced or metastatic differentiated thyroid cancer, a type of cancer in the thyroid gland, in adults when radioactive iodine and cancer medicines are no longer stopping the progression of the disease.

CABOMETYX may be given in combination with nivolumab for advanced kidney cancer. It is important that you also read the package leaflet for nivolumab. If you have any questions about these medicines, consult your doctor.

How CABOMETYX works

CABOMETYX blocks the action of proteins called tyrosine kinase receptors (RTKs), which are involved in cell growth and the development of new blood vessels that supply blood to these cells. These proteins may be present in high amounts in cancer cells, and by blocking their action, this medicine can slow down the rate at which the tumour grows and help disrupt the blood supply that the cancer needs.

2. What you need to know before taking CABOMETYX

Do not take CABOMETYX

• if you are allergic to cabozantinib or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before starting to take CABOMETYX:

• If you have high blood pressure.
• If you have or have had an aneurysm (a bulge and weakening in the wall of a blood vessel) or a tear in the wall of a blood vessel.
• If you have diarrhea.
• If you have recently experienced significant bleeding.
• If you have undergone surgery within the past month (or if you have surgery scheduled), including dental surgery.
• If you have inflammatory bowel disease (such as Crohn’s disease, ulcerative colitis, diverticulitis, or appendicitis).
• If you have recently had a blood clot in your leg, a stroke, or a heart attack.
• If you have thyroid problems. Inform your doctor if you feel more tired than usual, feel colder than others, or develop a deeper voice while taking this medicine.
• If you have liver or kidney disease.

Discuss with your doctor if any of the above apply to you.

You may require treatment, or your doctor may decide to adjust the dose of CABOMETYX or stop treatment completely. Also refer to section 4 "Possible side effects".

You should also inform your dentist that you are taking this medicine. It is important for you to maintain good oral hygiene during treatment.

Children and adolescents

The use of CABOMETYX is not recommended in children and adolescents. The effects of this medicine in individuals under 18 years of age are unknown.

Other medicines and CABOMETYX

Tell your doctor or pharmacist if you are taking, or have recently taken, any other medicines, including those obtained without a prescription. This is because CABOMETYX may affect how other medicines work. Likewise, some medicines may affect how CABOMETYX works. This may require your doctor to adjust your dose(s). You should inform your doctor about any medication, but particularly if you are taking:

• Medicines to treat fungal infections, such as itraconazole, ketoconazole, and posaconazole
• Medicines used to treat bacterial infections (antibiotics), such as erythromycin, clarithromycin, and rifampicin
• Medicines for allergies, such as fexofenadine
• Medicines to treat angina (chest pain due to inadequate blood supply to the heart), such as ranolazine
• Medicines used to treat epilepsy or seizures, such as phenytoin, carbamazepine, and phenobarbital
• Herbal remedies containing St. John’s wort (Hypericum perforatum), sometimes used to treat depression or depression-related conditions such as anxiety
• Anticoagulant medicines such as warfarin and dabigatran etexilate
• Medicines to treat high blood pressure or other heart conditions, such as aliskiren, ambrisentan, dabigatran etexilate, digoxin, talinolol, and tolvaptan
• Medicines for diabetes, such as saxagliptin and sitagliptin
• Medicines used to treat gout, such as colchicine
• Medicines used to treat HIV or AIDS, such as efavirenz, ritonavir, maraviroc, and emtricitabine
• Medicines used to prevent transplant rejection (cyclosporine) and cyclosporine-based treatment regimens for rheumatoid arthritis and psoriasis

CABOMETYX with food

Avoid consuming grapefruit-containing products throughout the duration of treatment with this medicine, as they may increase levels of this medicine in the blood.

Pregnancy, breastfeeding, and fertility

Pregnancy must be avoided during treatment with CABOMETYX. If you or your partner can become pregnant, you must use effective contraception during treatment and for at least four months after treatment ends. Speak with your doctor about which contraceptive methods are appropriate while taking this medicine (see also “Other medicines and CABOMETYX”).

Consult your doctor if you or your partner become pregnant, or if you or your partner plan to become pregnant, during treatment with this medicine.

Talk to your doctor BEFORE starting this medicine if you or your partner are considering or have already planned to have a child after treatment ends. Treatment with this medicine may affect fertility.

Women taking this medicine must discontinue breastfeeding during treatment and for at least four months after treatment ends, as cabozantinib and/or its metabolites may be excreted in breast milk and could harm the breastfed infant.

If you take this medicine while using oral contraceptives, oral contraception may become ineffective. You should also use a barrier method of contraception (e.g., condom or diaphragm) while taking this medicine and for a minimum of 4 months after treatment ends.

Driving and using machines

Exercise caution when driving or operating machinery. Be aware that treatment with CABOMETYX may cause fatigue or weakness and may affect your ability to drive or operate machinery.

CABOMETYX contains lactose

This medicine contains lactose (a type of sugar). If your doctor has informed you that you have an intolerance to certain sugars, consult with your doctor before taking this medicine.

CABOMETYX contains sodium

This medicine contains less than 1 mmol (23 mg of sodium) per tablet; this is essentially “sodium-free”.

3. How to take CABOMETYX

Follow exactly the instructions given by your doctor or pharmacist for taking this medicine. If in doubt, consult your doctor or pharmacist again.

Keep taking this medicine until your doctor decides to stop treatment. If you experience serious side effects, your doctor may decide to change the dose or stop treatment earlier than originally planned. Your doctor will tell you if a dose adjustment is necessary.

You must take CABOMETYX once daily. The usual dose is 60 mg; however, your doctor will decide the appropriate dose for you.

When this medicine is administered in combination with nivolumab for the treatment of advanced renal cell carcinoma, the recommended dose of CABOMETYX is 40 mg once daily.

Do not take CABOMETYX with food.

Do not eat for at least 2 hours before and for 1 hour after taking this medicine.

Swallow the tablet with a full glass of water. Do not crush the tablets.

If you take more CABOMETYX than you should

If you have taken more of this medicine than prescribed, speak to a doctor or go to hospital immediately, taking the tablets and this leaflet with you.

If you forget to take CABOMETYX

• If there are 12 or more hours until your next dose, take the missed dose immediately. Take your next dose at the usual time.
• If there are less than 12 hours until your next dose, do not take the missed dose. Take your next dose at the usual time.

If you stop taking CABOMETYX

Stopping your treatment may interrupt the effect of your medicine. Do not stop treatment with this medicine unless you have discussed it with your doctor.

When this medicine is administered in combination with nivolumab, nivolumab will be given first, followed by CABOMETYX.

Refer to the nivolumab package leaflet to understand how this medicine is used. If you have any further questions about the use of this medicine, ask your doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. If you experience adverse effects, your doctor may advise you to take CABOMETYX at a lower dose. Your doctor may also prescribe other medicines to help manage the adverse effects.

Contact your doctor immediately if you notice any of the following adverse effects, as you may require urgent medical treatment:

• Symptoms such as abdominal pain, nausea (feeling unwell), vomiting, constipation, or fever. These symptoms may be due to gastrointestinal perforation, a hole in the stomach or intestine, which can be life-threatening. Gastrointestinal perforation is common (may affect up to 1 in 10 people).
• Severe or uncontrollable bleeding, with symptoms such as blood in vomit, black stools, blood in urine, headache, or coughing up blood. This is common (may affect up to 1 in 10 people).
• Drowsiness, confusion, or loss of consciousness. These may be due to liver problems, which are common (may affect up to 1 in 10 people).
• Swelling or difficulty breathing. These are very common (may affect more than 1 in 10 people).
• A wound that does not heal. This is uncommon (may affect 1 in 100 people).
• Seizures, headache, confusion, or difficulty concentrating. These may be signs of a condition called reversible posterior encephalopathy syndrome (RPES). RPES is uncommon (may affect 1 in 100 people).
• Pain in the mouth, teeth, and/or jaw, swelling or sores in the mouth, numbness or a heavy sensation in the jaw, or a loose tooth. These may be symptoms of jaw bone damage (osteonecrosis). This is uncommon (may affect 1 in 100 people).

Other adverse effects with CABOMETYX when given alone may include:

Very common adverse effects (may affect more than 1 in 10 people)

• Anaemia (low levels of red blood cells that carry oxygen), low platelet count (cells that help blood to clot)
• Reduced thyroid activity, with symptoms such as tiredness, weight gain, constipation, feeling cold, and dry skin
• Decreased appetite, weight loss, altered sense of taste
• Reduced levels of magnesium, potassium, or calcium in the blood
• Reduced levels of the protein albumin in the blood (which transports substances such as hormones, medicines, and enzymes throughout the body)
• Headache, dizziness
• High blood pressure (hypertension)
• Bleeding
• Difficulty speaking, hoarseness (dysphonia), cough, and difficulty breathing
• Stomach problems such as diarrhoea, nausea, vomiting, constipation, indigestion, and abdominal pain
• Redness, swelling, or pain in the mouth or throat (stomatitis)
• Skin rash, sometimes with blisters, itching, pain in the hands or soles of the feet, rash
• Pain in arms, hands, legs, or feet, joint pain
• Feeling tired or weak, inflammation of the oral and gastrointestinal mucosa, swelling of arms and legs
• Weight loss
• Abnormal liver function tests (increased levels of liver enzymes aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase)

Common adverse effects (may affect up to 1 in 10 people)

• Abscess (collection of pus with swelling and inflammation)
• Dehydration
• Decreased levels of phosphate or sodium in the blood
• Increased levels of potassium in the blood
• Increased levels of the waste product bilirubin in the blood (which may cause jaundice/yellowing of the eyes or skin)
• Increased (hyperglycaemia) or decreased (hypoglycaemia) blood sugar levels
• Nerve inflammation (causing numbness, weakness, tingling, or burning in arms and legs)
• Ringing in the ears (tinnitus)
• Blood clots in veins, low blood pressure (hypotension)
• Blood clots in the lungs, inflammation of the nasal mucosa (allergic rhinitis)
• Pancreatitis (inflammation of the pancreas), painful tear or abnormal connection in body tissues (fistula), gastroesophageal reflux disease (acid reflux from the stomach), haemorrhoids (piles), dry mouth, mouth pain, difficulty swallowing, flatulence
• Intense itching of the skin, alopecia (hair loss and thinner hair), dry skin, acne, change in hair colour, thickening of the outer layer of skin, skin redness
• Muscle spasms
• Protein in urine (detected in tests)
• Abnormal liver function tests (increased levels of the liver enzyme gamma-glutamyl transferase in blood)
• Abnormal kidney function tests (increased levels of creatinine in blood)
• Increased levels of the enzyme that breaks down fats (lipase) and the enzyme that breaks down starch (amylase)
• Increased levels of cholesterol or triglycerides in blood
• Low white blood cell count (important for fighting infection)
• Lung infection (pneumonia)

Uncommon adverse effects (may affect up to 1 in 100 people)

• Seizures, stroke
• Severe increase in blood pressure
• Blood clots in arteries
• Reduced bile flow from the liver
• Pain or burning sensation on the tongue (glossodynia)
• Heart attack
• Blood clot/embolus that has travelled through your arteries and become lodged
• Lung collapse due to air leaking into the space between the lung and chest wall, often causing difficulty breathing (pneumothorax)

Frequency not known (proportion of affected people not known)

• Enlargement and weakening of a blood vessel wall or tear in the blood vessel wall (aneurysms and arterial dissections)
• Inflammation of blood vessels in the skin (cutaneous vasculitis)

The following adverse effects have been reported with CABOMETYX in combination with nivolumab:

Very common adverse effects (may affect more than 1 in 10 people)

• Upper respiratory tract infections
• Reduced thyroid activity; symptoms may include tiredness, weight gain, constipation, feeling cold, and dry skin
• Increased thyroid activity; symptoms may include rapid heartbeat, sweating, and weight loss
• Decreased appetite, altered sense of taste
• Headache, dizziness
• High blood pressure (hypertension)
• Difficulty speaking, hoarseness (dysphonia), cough, and difficulty breathing
• Stomach discomfort, including diarrhoea, nausea, vomiting, indigestion, abdominal pain, and constipation
• Redness, swelling, or pain in the mouth or throat (stomatitis)
• Skin rash, sometimes with blisters, itching, pain in the hands or soles of the feet, rash, or intense skin itching
• Joint pain (arthralgia), muscle spasms, muscle weakness, and muscle pain
• Protein in urine (detected in tests)
• Feeling tired or weak, fever, and oedema (swelling)
• Abnormal liver function tests (increased levels of liver enzymes aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase in blood, elevated blood levels of bilirubin waste product)
• Abnormal kidney function tests (increased creatinine in blood)
• High (hyperglycaemia) or low (hypoglycaemia) blood sugar levels
• Anaemia (low red blood cell levels (which carry oxygen), low white blood cell levels (important for fighting infection), low platelet levels (cells that help blood to clot))
• Elevated levels of the enzyme that breaks down fats (lipase) and the enzyme that breaks down starch (amylase)
• Decreased phosphate levels
• Increased or decreased potassium levels
• Decreased or increased levels of calcium, magnesium, or sodium in blood
• Decreased body weight

Common adverse effects (may affect up to 1 in 10 people)

• Severe lung infection (pneumonia)
• Increase in certain white blood cells called eosinophils
• Allergic reaction (including anaphylactic reaction)
• Decreased secretion of hormones produced by the adrenal glands (glands located above the kidneys)
• Dehydration
• Nerve inflammation (causing numbness, weakness, tingling, or burning in arms and legs)
• Ringing in the ears (tinnitus)
• Dry eyes and blurred vision
• Changes in heart rhythm or rate, rapid heartbeat
• Blood clots in blood vessels
• Lung inflammation (pneumonitis, characterized by cough and difficulty breathing), blood clots in the lung, fluid around the lungs
• Nosebleeds
• Inflammation of the colon (colitis), dry mouth, mouth pain, stomach inflammation (gastritis), and haemorrhoids (piles)
• Liver inflammation (hepatitis)
• Dry skin and skin redness
• Alopecia (hair loss and thinner hair), change in hair colour
• Joint inflammation (arthritis)
• Kidney failure (including sudden loss of kidney function)
• Pain, chest pain
• Increased levels of triglycerides in blood
• Increased levels of cholesterol in blood

Uncommon adverse effects (may affect 1 in 100 people)

• Allergic reactions related to the infusion of nivolumab
• Inflammation of the pituitary gland at the base of the brain (hypophysitis), inflammation of the thyroid gland (thyroiditis)
• Temporary nerve inflammation causing pain, weakness, and paralysis in limbs (Guillain-Barré syndrome); muscle weakness and fatigue without atrophy (myasthenic syndrome)
• Brain inflammation
• Eye inflammation (causing pain and redness)
• Inflammation of the heart muscle
• Blood clot/embolus that has travelled through your arteries and become lodged
• Pancreatitis (inflammation of the pancreas), intestinal perforation, burning or painful sensation on the tongue (glossodynia)
• Skin disease with thickened areas of red skin, often with silvery scales (psoriasis)
• Hives (itchy rash)
• Feeling of muscle weakness not caused by exercise (myopathy), jaw bone damage, painful tear or abnormal connection in body tissues (fistula)
• Kidney inflammation
• Lung collapse due to air leaking into the space between the lung and chest wall, often causing difficulty breathing (pneumothorax)

Frequency not known (proportion of affected people not known)

• Inflammation of blood vessels in the skin (cutaneous vasculitis)
• Progressive destruction and loss of intrahepatic bile ducts and jaundice

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of CABOMETYX

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the blister, and on the label of the bottle and carton after EXP. The expiry date is the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging when they are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

Composition of CABOMETYX

The active substance is (S)-cabozantinib malate.

CABOMETYX 20 mg film-coated tablets: each tablet contains (S)-cabozantinib malate, equivalent to 20 mg of cabozantinib.

CABOMETYX 40 mg film-coated tablets: each tablet contains (S)-cabozantinib malate, equivalent to 40 mg of cabozantinib.

CABOMETYX 60 mg film-coated tablets: each tablet contains (S)-cabozantinib malate, equivalent to 60 mg of cabozantinib.

The other components are:

• Tablet core: microcrystalline cellulose, anhydrous lactose, hydroxypropylcellulose, sodium croscarmellose, colloidal anhydrous silica, magnesium stearate. (see section 2 for lactose content)
• Film coating: hypromellose 2910, titanium dioxide (E171), triacetin, yellow iron oxide (E172)

Appearance of CABOMETYX and pack contents

CABOMETYX 20 mg film-coated tablets are yellow, round, film-coated tablets without a breakline, marked with « XL » on one side and « 20 » on the other.

CABOMETYX 40 mg film-coated tablets are yellow, triangular, film-coated tablets without a breakline, marked with « XL » on one side and « 40 » on the other.

CABOMETYX 60 mg film-coated tablets are yellow, oval, film-coated tablets without a breakline, marked with « XL » on one side and « 60 » on the other.

CABOMETYX is available in packs containing one plastic bottle with 30 film-coated tablets.

The bottle contains three silica gel desiccant containers and a polyester wad to prevent damage to the film-coated tablets. Keep these desiccant containers and the polyester wad in the bottle and do not swallow them.

Marketing Authorisation Holder

Ipsen Pharma

70 rue Balard

75015 Paris

France

Manufacturer

Patheon France

40 Boulevard de Champaret

38300 Bourgoin Jallieu, France

Tjoapack Netherlands B.V.

Nieuwe Donk 9

4879 AC Etten-Leur

The Netherlands

Rottendorf Pharma GmbH

Ostenfelderstrasse 51 – 61

D-59320 Ennigerloh, Germany

Further information on this medicinal product can be requested by contacting the local representative of the Marketing Authorisation Holder.

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.